title: Relationship of ketamine's antidepressant and psychotomimetic effects in unipolar depression.
abstract: OBJECTIVE
  Ketamine and other NMDA (N-methyl-D-aspartate) antagonists produce fast-acting antidepressant-like effects, although the underlying mechanism is unclear. Furthermore, high affinity NMDA antagonists such as ketamine are associated with psychotomimetic effects. To date the link between the antidepressant and psychotomimetic effects of ketamine has not been explored. We examined the relationship between the antidepressant and psychotomimetic effects of a single ketamine infusion in subjects diagnosed with major depressive disorder.
  
  
  METHODS
  In a double-blind, cross-over, placebo-controlled, two weeks clinical trial we studied the effects of ketamine (0.54 mg/kg within 30 min) in a group of 27 hospitalized depressive patients.
  
  
  RESULTS
  Higher intensity of psychotomimetic symptoms, measured using BPRS, during ketamine administration correlated with alleviation in mood ratings during the following week with maximum on day seven. Ketamine was superior to placebo in all visits (day 1, 4, and 7) assessed by MADRS with effect size (Cohen´s d) of 0.62, 0.57, and 0.44 respectively. There was no significant correlation between ketamine and nor-ketamine plasma levels and MADRS score change at any study time point.
  
  
  CONCLUSIONS
  The substantial relationship between ketamine's antidepressant and psychotomimetic effects was found. This relationship could be mediated by the initial steps of ketamine's action, trough NMDA receptors, shared by both ketamine's clinical effects.
authors.affiliation: Prague Psychiatric Centre, Prague, Czech Republic. sos@pcp.lf3.cuni.cz
authors.forename: Peter
authors.initials: P
authors.lastname: Sos
authors.forename: Monika
authors.initials: M
authors.lastname: Klirova
authors.forename: Tomas
authors.initials: T
authors.lastname: Novak
authors.forename: Barbora
authors.initials: B
authors.lastname: Kohutova
authors.forename: Jiri
authors.initials: J
authors.lastname: Horacek
authors.forename: Tomas
authors.initials: T
authors.lastname: Palenicek
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D018592:Cross-Over Studies; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006213:Hallucinogens / Q000627:therapeutic use*; D006801:Humans; D007262:Infusions, Intravenous; D007649:Ketamine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D006213:Hallucinogens; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine